Research ScientistKoch Institute for Integrative Cancer Research Manalis Lab

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Weighing particles at the attogram scale

Naturally occurring and engineered nanoparticles (e.g., exosomes, viruses, protein aggregates, and self-assembled nanostructures) have size- and concentration-dependent functionality, yet existing characterization methods in solution are limited for diameters below ∼50 nm. Here, we developed a mechanical resonator that can directly measure the mass of individual nanoparticles down to 10 nm in solution with single-attogram (one billionth of a billionth of a gram or ~600 kilodaltons) precision, enabling access to previously difficult-to-characterize natural and synthetic nanoparticles.

The device builds on a technology developed for weighing single cells. This device, known as a suspended microchannel resonator (SMR), measures the particles' mass as they flow through a narrow channel buried inside of a vibrating cantilever. As the cells travel through the narrow channel, the vibration frequency of the cantilever transiently changes due to the additional mass of the cell. By measuring the frequency changes, we can precisely calculate the mass of particles in solution. For weighing nanosized particles using the same approach, we shrank the size of the cantilever, so that the integrated microfluidic channel has a cross section of 400 nm by 1 micron. This way we were able to weigh nanoparticles with 0.85 attograms precision. We call this new device, suspended nano-channel resonators, due to its capability of weighing nanoparticles down to 10 nm in size.

In addition to testing our device by weighing gold nanoparticles, we analyzed a type of biological nanoparticles called exosomes — vesicles that carry proteins, RNA, or other molecules secreted by cells — which are believed to play a role in signaling between distant locations in the body. We found that exosomes secreted by liver cells and fibroblasts (cells that make up connective tissue) had different profiles of mass distribution, suggesting that it may be possible to distinguish vesicles that originate from different cells and may have different biological functions. We are now investigating if precise measurement of mass profiles of extracellular vesicles in body fluids can provide clinically relevant information about various diseases.